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    Four Essays On Virgin Islands Literature

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    Through close reading, historical analysis, and creative vignettes, I explore how authors and artists in the Virgin Islands have responded to ongoing American colonial rule. I suggest that these Virgin Islands authors and artists challenge postcolonial sovereignty as the only available political horizon. Chapter one juxtaposes the St. Croix Labor Union’s newspaper, The Herald, with a series of historic photographs to constitute an alternative archive that places black life at the center of American imposition in 1917. Chapter two demonstrates how playwrights have mobilized the history of revolutionary labor struggle against Danish colonialism and slavery in the nineteenth century to interpret twentieth century American empire. Chapter three explores how Tiphanie Yanique’s novel, Land of Love and Drowning, represents intimacy and desire as forces that can challenge the bounds of American imperialism. Chapter four considers how the lyrics of singer-songwriter Vaughn Benjamin shift the discussion of non-sovereignty from the state to the human, offering a revitalized humanism grounded in Rastafari philosophy and non-sovereign human agency. Together, these essays suggest that the Virgin Islands is not a site of exception, but crucial to broadening understandings of Anglocreole Caribbean literature and postcolonial sovereignty

    Three Essays On Internal Migration And Risk Factors For Non-Communicable Diseases (ncds) In Low- And Middle-Income Countries (lmics)

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    Low- and middle-income countries (LMICs) have been experiencing extensive internal migration, which is closely associated with the increasing prevalence of risk factors for non-communicable diseases (NCDs). In this dissertation, I study the impact of internal migration on main NCD risk factors across three diverse LMIC contexts: China, Indonesia, and Malawi. In Chapter 1, I introduce the background, motivation, and research goals of this dissertation. In Chapter 2, I use data from the 2011 China Health and Retirement Longitudinal Study (CHARLS) to examine the associations between rural-urban migration and three main NCD risk factors, hypertension, obesity, and abdominal obesity, among older adults aged 45 or above. I find that rural-urban migrants have significantly higher chances of getting all three risk factors than rural non-migrants, suggesting a negative impact of rural-urban migration on health outcomes. Meanwhile, the number of years lived in cities significantly predicts being hypertensive, implying a “years since migration (YSM)” effect. In addition, health-related behaviors examined play a very limited role in mediating the association between migration and health. In Chapter 3, using data from the fourth and fifth waves of the Indonesia Family Life Survey (IFLS), I study the impact of rural-urban migration on overweight status in Indonesia. I find that rural-urban migration is significantly associated with being overweight, and the association is significantly stronger among women than men, demonstrating a gender disparity in health. Moreover, the number of years lived in cities does not predict overweight status, and health behavioral factors still explain little of the association between migration and health. In Chapter 4, I use data from the 2008 and 2019 waves of the Malawi Longitudinal Study of Families and Health (MLSFH) to investigate the impact of internal migration, not only rural-urban but also rural-rural, on weight status in Malawi. I find that rural-urban and rural-rural migration are both significantly associated with increased Body Mass Index (BMI) and that rural-rural migration significantly predicts being overweight. Meanwhile, the impact of rural-rural migration is significantly stronger among women than men, showing a gendered impact of migration on health. In Chapter 5, I summarize findings from the three main chapters and discuss their implications for policymaking and future research

    Disorderly And Inhumane: Explaining Government-Sponsored Mass Expulsion, 1900-2020

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    Since 2015 over two million people have been expelled, en masse, around the world. Mass expulsion is a major international issue that threatens peace and security around the globe. This dissertation examines why and how governments expel ethnic groups en masse. What motivates them to implement an expulsion policy and why don’t more governments do the same? By isolating policies of intentional group-based population removal—distinct from genocide, massacre, and coercive assimilation—I show that the motivations of expulsionist governments are informed by the phase of nation-building and the perceived threat of the target group. The four clusters of motivations are: fifth column, anti-colonialism, nativism, and counterinsurgency/reprisal. Since not all governments with one of the identified motivations to expel go on to remove populations en masse, I also identify important constraints on governments’ strategic choices. Through four paired-comparison case studies of similarly motivated governments with different outcomes (expulsion or non-expulsion), I show that alliances, target group homeland state(s), and the international community are the key contributing factors that enable or deter mass expulsion policies. The evidence is drawn from archival research conducted at the United Nations High Commissioner for Refugees, the International Committee of the Red Cross, and the League of Nations archives in Geneva, Switzerland, as well as from other primary sources, secondary historical sources, and extant datasets. This dissertation contributes to the field of ethnic conflict and exclusionary politics. It fills a gap in the literature by systematically examining mass expulsion policies that intentionally remove ethnic groups over the longue durée. The argument expands existing explanations beyond war and security threats to highlight an entire class of expulsions that target economic threats, which requires scholarly and international policy attention. The dissertation also deepens our understanding of critical atrocity constraints and proposes tangible policy recommendations for deterring its use

    Complex Systems Engineering: Designing Advanced Functions In Dynamical And Mechanical Systems

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    From computation in neural networks to allostery in proteins, numerous natural and artificial systems are comprised of many interacting parts that give rise to advanced functions. To study such complex systems, a diverse array of interdisciplinary tools have been developed that relate the interactions of existing systems to their functions. However, engineering the interactions to perform designed functions in novel systems remains a significant challenge due to the nonlinearities in the interactions and the vast dimensionality of the design space. Here we develop design principles for complex dynamical and mechanical systems at the lowest level of their microstate interactions. In dynamical neural systems, we use methods from control theory and dynamical systems theory to mathematically map precise patterns of neural connectivity to the control of neural states in human and non-human brains (Chapter 2) and to the learning of computations on internal representations in artificial recurrent neural networks (Chapter 4). In mechanical systems, we use methods from algebraic geometry and dynamical systems to mathematically map precise patterns of mechanical constraints to design shape changes as a minimal model of protein allostery and cooperativity (Chapter 6) and to engineer mechanical metamaterials that possess arbitrarily complex shape changes (Chapter 8). These intuitive maps allow us to navigate previously unexplored design spaces in nonlinear and high-dimensional regimes, enabling us to reverse engineer form from function in novel complex systems that have yet to exist

    Engineering Controllable And Efficient Base Editors By Targeted Manipulation Of Dna Deaminases

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    Base editors (BEs) combine DNA deaminase mutator activity with CRISPR-Cas localization to create targeted point mutations in genomic DNA. Current approaches with BEs have enabled single-base alterations for several applications, including modeling and correction of disease alleles, crop engineering, and gene diversification. However, two major challenges limit their applicability: (1) moderate editing efficiency and (2) off-target mutagenesis of DNA and RNA. Here, we leverage our mechanistic knowledge into DNA deaminases to separately address both challenges. For one, nature has evolved DNA deaminases with suboptimal activity to achieve their role in immunity and minimize genomic instability. By deriving and characterizing hyperactive deaminases, I revealed intrinsic deaminase activity as a rate-limiting step in the base-editing reaction. Interestingly, hyperactive deaminases also had a broadened activity window, revealing a tradeoff between efficiency and precision. By harnessing their broad activity and skewing repair, we developed novel diversifying BEs that generate simultaneous C\u3eT and G\u3eA mutations efficiently over an expanded editing window of more than 65 bp. Second, DNA deaminases are highly regulated to achieve purposeful mutagenesis in physiological settings. Inspired by nature, I aimed to build regulatory control into the activity of DNA deaminases by splitting the enzyme into two inactive fragments, whose reapproximation reconstitute activity. This finding allowed me to develop small-molecule-inducible split-engineered base editors, which show decreased off-target editing when compared to intact BEs and newly enable temporal control over precise genome editing. Third, understanding the mechanistic basis for the preferential targeting of deaminases for DNA over RNA could provide means for engineering variants with decreased reactivity towards RNA. Thus, we developed biochemical assays to characterize the activity of AID/APOBEC enzymes on both substrates. Focusing on APOBEC3A, we establish the target base as a major determinant of selectivity and demonstrate that although overall deamination is greatly reduced in RNA, there is a strong selectivity for idealized substrates. Altogether, my results offer mechanistic insights into the incorporation of DNA deaminases in BEs, facilitating the development of enhanced base editing tools for diverse applications

    Visual-Inertial State Estimation With Information Deficiency

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    State estimation is an essential part of intelligent navigation and mapping systems where tracking the location of a smartphone, car, robot, or a human-worn device is required. For autonomous systems such as micro aerial vehicles and self-driving cars, it is a prerequisite for control and motion planning. For AR/VR applications, it is the first step to image rendering. Visual-inertial odometry (VIO) is the de-facto standard algorithm for embedded platforms because it lends itself to lightweight sensors and processors, and maturity in research and industrial development. Various approaches have been proposed to achieve accurate real-time tracking, and numerous open-source software and datasets are available. However, errors and outliers are common due to the complexity of visual measurement processes and environmental changes, and in practice, estimation drift is inevitable. In this thesis, we introduce the concept of information deficiency in state estimation and how to utilize this concept to develop and improve VIO systems. We look into the information deficiencies in visual-inertial state estimation, which are often present and ignored, causing system failures and drift. In particular, we investigate three critical cases of information deficiency in visual-inertial odometry: low texture environment with limited computation, monocular visual odometry, and inertial odometry. We consider these systems under three specific application settings: a lightweight quadrotor platform in autonomous flight, driving scenarios, and AR/VR headset for pedestrians. We address the challenges in each application setting and explore how the tight fusion of deep learning and model-based VIO can improve the state-of-the-art system performance and compensate for the lack of information in real-time. We identify deep learning as a key technology in tackling the information deficiencies in state estimation. We argue that developing hybrid frameworks that leverage its advantage and enable supervision for performance guarantee provides the most accurate and robust solution to state estimation

    Central Control Of Pain And Inflammation Through A Hunger Circuit

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    Homeostasis is established through bidirectional communication between the periphery and the central nervous system. To maintain homeostasis, some biological drives can become prioritized over others. This changing balance between biological drives encourages peak performance and survival. However, when homeostasis is disturbed, chronic inflammatory diseases such as obesity, chronic pain, and arthritis can arise. We became interested in understanding if competing biological drives could be leveraged for therapeutic purposes. Food restriction inhibits inflammation; therefore, we explored how hunger and feeding neural circuits affect responses to noxious agents. Our first study investigated the role of hunger to alleviate pain behavior. We found that hunger significantly reduces time spent licking during the inflammatory phase of a formalin pain assay but leaves intact pain responses to acute threats. We next evaluated if hypothalamic hunger neurons are involved in this behavioral change. Stimulation of agouti-related protein expressing (AgRP) neurons significantly reduced formalin pain behavior. To determine the central nodes that mediate this effect, we systematically screened AgRP neuron projections for their ability to suppress pain. Only AgRP neurons projecting to the hindbrain parabrachial nucleus was able to reduce inflammatory pain behavior. Our second study investigated the role of hunger to influence inflammatory responses of an injury site. Using two models of localized inflammation, we found that food deprivation robustly reduces inflammation, pro-inflammatory cytokine levels, and associated temperature increases induced by injection of noxious stimuli [complete Freund’s adjuvant (CFA) or formalin]. Activation of AgRP neurons recapitulated the effect of food deprivation on inflammation. We then evaluated the role of each AgRP axonal target structure to reduce inflammation. Interestingly, stimulation of AgRP neurons that project to the paraventricular nucleus of the hypothalamus or the parabrachial nucleus were sufficient to reduce CFA-induced inflammation. Finally, we identified the vagus nerve as a key pathway for the anti-inflammatory effect of hunger. We propose that hunger, through AgRP neurons, inhibits pro-inflammatory responses from the central nervous system and changes the output of efferent vagal fibers. This body of work reveals a central node for the reduction of pain and inflammation, highlighting a novel role for hypothalamic circuits to influence injury responses

    Lesker PVD75 E-beam Evaporator (PVD-04) Standard Operating Procedure

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    Standard Operating Procedure for the Lesker PVD75 E-beam Evaporator (PVD-04) located at the Quattrone Nanofabrication Facility within the Singh Center for Nanotechnology at the University of Pennsylvaniahttps://repository.upenn.edu/scn_sop/1024/thumbnail.jp

    Essays On The Role Of Information In Health Economics

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    This dissertation is comprised of essays on the role of information in health economics. In the first chapter, I study quality ratings. Ratings provide consumers with useful quality information, however, when ratings shift demand to highly-rated sellers, congestion might occur at the top of the quality distribution. Congestion caused by disclosure may be observed in the health care setting, where prices often cannot adjust to reflect varying quality. I study the trade-off between providing quality information for consumers and congestion using a star rating disclosure policy implemented at a large integrated health system in the United States, which requires every physician to have star ratings posted online in a standardized fashion. I identify the effects of physician star ratings on patient volume using a regression discontinuity and difference-in-discontinuity design which leverages the rounding of ratings to discrete values and the fact that I observe ratings before and after their public disclosure online. I find that an increase in a physician\u27s rating increases the number of new patients seen by 2.96 visits per month on a baseline of 5.48 (54% increase). I show that star ratings shift patients to physicians who more often provide medically recommended screenings, counseling, and vaccinations. However, I also show that a higher rating causes patients to wait longer for treatment. New patients wait 2.7 additional days (30.5% longer) for an additional increment of the rating scale and existing patients wait longer as well. I use these findings to compute a revealed-preference estimate of the shadow price of a star ; I find that patients are willing to wait 3 additional days in exchange for a one standard deviation increase in physician ratings. In the absence of a price, wait times may serve as an equilibrating factor to clear the market. In the second chapter, I study surprise medical bills. I introduce a model of final-offer arbitration over these bills between insurers and providers which highlights the tradeoffs for firms and policymakers

    Understanding The Role Of Nuclear Acetyl-Coa Synthetase 2 In Maintaining Histone Acetylation

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    Histone acetylation is governed by nuclear acetyl-CoA pools generated in part from local acetate by metabolic enzyme acetyl-CoA synthetase 2 (ACSS2). We hypothesize that during gene activation, a local transfer of intact acetate occurs via sequential action of epigenetic and metabolic enzymes. Using stable isotope labeling, we detect transfer between histone acetylation sites both in vitro using purified mammalian enzymes and in vivo using quiescence exit in Saccharomyces cerevisiae as a change-of-state model. We show that Acs2, the yeast orthologue of ACSS2, is recruited to chromatin during quiescence exit, and observe dynamic histone acetylation changes proximal to Acs2 peaks. We find that Acs2 is preferentially associated with the most upregulated genes, suggesting that acetyl-group transfer plays an important role in gene activation. Overall, our data reveal direct transfer of acetate between histone lysine residues to facilitate rapid transcriptional induction, an exchange that may be critical during changes in nutrient availability.Since ACSS2 does not have known DNA- or histone-binding domains, we hypothesize that it associates with chromatin indirectly through other transcription factors or chromatin modifying enzymes. We performed immunoprecipitation experiments coupled to mass spectrometry in neuronal cell lines and mouse models and identified nuclear accumbens associated 1 (NACC1) as a novel interactor. We determined nuclear localization of both ACSS2 and NACC1 in differentiated cells through proteomics experiments. Moreover, we have found ACSS2 and NACC1 chromatin-bound during differentiation and enriched near genes of cell-cell adherens, cytoplasmic, and membrane, which are important in differentiation and formation of neuronal processes. Our findings highlight a potential mechanism for ACSS2 recruitment to during critical metabolic changes such as neuronal differentiation

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